A biallelic gene polymorphism of CYP11B2 predicts increased aldosterone to renin ratio in selected hypertensive patients.
J Clin Endocrinol Metab
; 88(6): 2495-500, 2003 Jun.
Article
em En
| MEDLINE
| ID: mdl-12788845
ABSTRACT
Altered control of aldosterone synthase (CYP11B2) gene expression may modulate aldosterone secretion, as suggested by a raised aldosterone to renin ratio (ARR) in some patients with essential hypertension. We compared the frequency of two linked CYP11B2 polymorphisms, one in the steroidogenic factor-1 (SF-1) binding site and the other an intronic conversion (Int2) in relation to ARR in 141 hypertensive patients. Patients were divided into groups with either normal or high supine ARR using a cut-off threshold of 145 pmol/liter per ng/liter. Supine ARR was normal in 104 patients and raised in 37 patients. The two polymorphisms were in strong linkage disequilibrium (chi(2) = 123.8; P < 0.0001). The SF-1 T and Int2 C alleles were more prevalent among patients with high ARR (46% and 43%, respectively) than with normal ARR (22% and 17%; P < 0.01 and P < 0.005, respectively). Odds ratios for raised ARR in subjects with a homozygous SF-1 T and Int2 C haplotype were 6.1 (95% confidence interval, 1.6-22.5; P < 0.005) when compared with the contrasting haplotype. Linear modeling of individual postural changes in renin and aldosterone showed a maximal achievable aldosterone increase of 110 pmol/liter with no mutated haplotype and 500 pmol/liter with two mutated haplotypes. These findings support the view of a molecular basis regulating aldosterone production.
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Base de dados:
MEDLINE
Assunto principal:
Renina
/
Citocromo P-450 CYP11B2
/
Aldosterona
/
Hipertensão
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article